Tumor microenvironment-responsive gold nanodendrites for nanoprobe-based single-cell Raman imaging and tumor-targeted chemo-photothermal therapy

Nanodendrite particles (NDs) with densely branched structures and biomimetic architectures have exhibited great promise in tumor therapy owing to their prolonged in vivo circulation time and exceptional photothermal efficiency. Nevertheless, traditional NDs are deficient in terms of specific surface modification and targeting tumors, which restricts their potential for broader clinical applications. Here, we developed coronavirus-like gold NDs through a seed-mediated approach and using silk fibroin (SF) as a capping agent. Our results demonstrate that these NDs have a favorable drug-loading capacity (∼65.25%) and light-triggered release characteristics of doxorubicin hydrochloride (DOX). Additionally, NDs functionalized with specific probes exhibited exceptional surface-enhanced Raman scattering (SERS) characteristics, enabling high-sensitivity Raman imaging of unstained single cells. Moreover, these NDs allowed for real-time monitoring of endocytic NDs for over 24 h. Furthermore, ND@DOX conjugated with tumor-targeting peptides exhibited mild hyperthermia, minimal cytotoxicity, and effective targeting towards cancer cells in vitro, as well as responsiveness to the tumor microenvironment (TME) in vivo. These unique properties led to the highest level of synergistic tumor-killing efficiency when stimulated by a near-infrared (NIR) laser at 808 nm. Therefore, our virus-like ND functionalized with SF presents a novel type of nanocarrier that exhibits significant potential for synergistic applications in precision medicine.

Viruses as biomaterials

Viruses lacking the capacity to infect mammals exhibit minimal toxicity, good biocompatibility, and well-defined structures. As self-organized biomolecular assemblies, they can be produced from standard biological techniques on a large scale at a low cost. Genetic, chemical, self-assembly, and mineralization techniques have been applied to allow them to display functional peptides or proteins, encapsulate therapeutic drugs and genes, assemble with other materials, and be conjugated with bioactive molecules, enabling them to bear different biochemical properties. So far, a variety of viruses (infecting bacteria, plants, or animals), as well as their particle variants, have been used as biomaterials to advance human disease prevention, diagnosis, and treatment. Specifically, the virus-based biomaterials can serve as multifunctional nanocarriers for targeted therapy, antimicrobial agents for infectious disease treatment, hierarchically structured scaffolds for guiding cellular differentiation and promoting tissue regeneration, versatile platforms for ultrasensitive disease detection, tissue-targeting probes for precision bioimaging, and effective vaccines and immunotherapeutic agents for tackling challenging diseases. This review provides an in-depth discussion of these exciting applications. It also gives an overview of the viruses from materials science perspectives and attempts to correlate the structures, properties, processing, and performance of virus-based biomaterials. It describes the use of virus-based biomaterials for preventing and treating COVID-19 and discusses the challenges and future directions of virus-based biomaterials research. It summarizes the progressive clinical trials of using viruses in humans. With the impressive progress made in the exciting field of virus-based biomaterials, it is clear that viruses are playing key roles in advancing important areas in biomedicine such as early detection and prevention, drug delivery, infectious disease treatment, cancer therapy, nanomedicine, and regenerative medicine. [ FROM AUTHOR] Copyright of Materials Science & Engineering: R is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis.

Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HR-ESI-MS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3'-C-8'') biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak SARS-CoV-2 3CLpro inhibitory activity with 43 % inhibition rate at 40 µM.

The epidemiological features of respiratory tract infection using the multiplex panels detection during COVID-19 pandemic in Shandong province, China.

Respiratory tract infection is one of the most common reasons for both morbidity and mortality worldwide. High attention has been paid to the etiological tracing of respiratory tract infection since the advent of COVID-19. In this study, we aimed to evaluate the epidemiological features of pathogens in respiratory tract infection, especially during COVID-19 pandemic. A total of 7668 patients with respiratory tract infection who admitted to Qilu Hospital of Shandong University from March 2019 to Dec 2021 were retrospectively included. The respiratory tract specimens were detected using a commercial multiplex PCR-based panel assay for common respiratory pathogens including influenza A virus (Flu-A), influenza A virus H1N1 (H1N1), influenza A virus H3N2 (H3N2), influenza B virus (Flu-B), parainfluenza virus (PIV), respiratory syncytial virus (RSV), adenovirus (ADV), Boca virus (Boca), human Rhinovirus (HRV), Metapneumovirus (MPV), Coronavirus (COV), Mycoplasma pneumoniae (MP), and Chlamydia (Ch). The positive rates were compared using a chi-square test. Compared with 2019, the positive rate of pathogen detection during from January 2020 to December 2021 was significantly lower, especially the detection of Flu-A. The positive rate of respiratory pathogen strains was 40.18% during COVID-19 pandemic, and a total of 297 cases (4.69%) of mixed infection with two or more pathogens were detected. There was no statistical difference in the positive rate between male and female patients. However, the positive rates of infection were different among different age groups, with higher incidence of RSV in infancy and toddler group, and MP infection in children and teenager group. While, HRV was the most common pathogen in the adult patients. Moreover, Flu-A and Flu-B were higher in winter, and MP and RSV were higher in spring, autumn and winter. The pathogens such as ADV, BOCA, PIV, and COV were detected without significant seasonal distribution. In conclusion, respiratory pathogen infection rates may vary by age and season, regardless of gender. During the COVID-19 epidemic, blocking transmission routes could help reduce the incidence of respiratory tract infection. The current prevalence of respiratory tract infection pathogens is of great significance for clinical prevention, diagnosis and treatment.

Targeting viral proteins for restraining SARS-CoV-2: focusing lens on viral proteins beyond spike for discovering new drug targets.

INTRODUCTION: Emergence of highly infectious SARS-CoV-2 variants are reducing protection provided by current vaccines, requiring constant updates in antiviral approaches. The virus encodes four structural and sixteen nonstructural proteins which play important roles in viral genome replication and transcription, virion assembly, release , entry into cells, and compromising host cellular defenses. As alien proteins to host cells, many viral proteins represent potential targets for combating the SARS-CoV-2. AREAS COVERED: Based on literature from PubMed and Web of Science databases, the authors summarize the typical characteristics of SARS-CoV-2 from the whole viral particle to the individual viral proteins and their corresponding functions in virus life cycle. The authors also discuss the potential and emerging targeted interventions to curb virus replication and spread in detail to provide unique insights into SARS-CoV-2 infection and countermeasures against it. EXPERT OPINION: Our comprehensive analysis highlights the rationale to focus on non-spike viral proteins that are less mutated but have important functions. Examples of this include: structural proteins (e.g. nucleocapsid protein, envelope protein) and extensively-concerned nonstructural proteins (e.g. NSP3, NSP5, NSP12) along with the ones with relatively less attention (e.g. NSP1, NSP10, NSP14 and NSP16), for developing novel drugs to overcome resistance of SARS-CoV-2 variants to preexisting vaccines and antibody-based treatments.

Nanotechnology for ultrafast nucleic acid amplification

Nucleic acid detection has been one of the most valued tools in point-of-care diagnostics from life science, agriculture, food safety and environmental surveillance, because of its high sensitivity, great specificity and simple operation. Since polymerase chain reactions (PCR) were discovered, more and more researchers attach importance to exploring ultrafast nucleic acid amplification methods for further expediting the process of detection and curbing infectious diseases' high spread rate, especially after the coronavirus disease 2019 (COVID-19) worldwide pandemic event. Nowadays, nanotechnology as one of the most cutting-edge technologies has aroused growing attention. In this review, we describe new advances in nanotechnology research for ultrafast nucleic acid amplification. We have introduced commonly used nanotechnologies, namely nanofluidics, nanoporous materials, nanoparticles and so on. Recent advances in these nanotechnologies for ultrafast sample pretreatments, accelerated enzymatic amplification and rapid heating/cooling processes was summarized. Finally, challenges and perspectives for the future applications of ultrafast nucleic acid amplification are presented.

Willingness to accept herpes zoster vaccines and the influencing factors in China.

BACKGROUND: Herpes zoster increases the burden on the elderly in an aging society. Although an effective vaccine licensed by China Food and Drug Administration in 2019 was introduced into the market in June 2020, the willingness and influencing factors of herpes zoster vaccines in Chinese adults ≥ 50-years-old during coronavirus disease-2019 pandemic are yet to be elucidated. METHODS: An online questionnaire survey was conducted using a simple random sampling method in October 2021 for viewers of the broadcast program. A binary logistic regression and multiple response analysis were conducted for herpes zoster vaccine and vaccination willingness. Pareto's graphs were plotted to present the multiple-choice questions of influencing factors. RESULTS: A total of 3838 eligible participants were included in this study. Among them, 43.02% intended to be vaccinated, including 10.34% self-reported about receiving at least one shot of shingles vaccine, 30.22% declined, and 26.76% were hesitant. This population comprised a large proportion of middle-aged and older people (≥ 50-years-old) who have not experienced an episode of herpes zoster (54.98%) or are unaware of the virus (33.22%). The strongest determinants of vaccine hesitancy among older people were education background of Master's degree or above compared to senior high or equivalent and below, personal monthly income < 3000 RMB compared to 3000-5999 RMB, and living in a rural area. CONCLUSIONS: The willingness to get shingles vaccines can be improved further. Professional education and credible recommendation might prompt the elderly to improve their willingness and reassure them of the safety and efficacy of the vaccine. Also, accessibility and affordability should also be improved in the future.

Factor structure and measurement invariance of the Chinese version of the COVID-19 Phobia Scale in depressive symptoms sample during COVID-19 closure: An exploratory structural equation modeling approach

The COVID-19 Phobia Scale is an instrument for measuring the phobia of coronavirus. It has a stable four-factor structure and good reliability and validity in other countries and regions. In order to expand related research, this study aims to test the reliability and validity of the COVID-19 Phobia Scale in Chinese adolescents with depressive symptoms. The C19P-SC was translated into Chinese by the method of forward and back translation and tested in 1933 Chinese adolescents with depressive symptoms. Confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM) were used to test and compare the four-factor model of the C19P-SC. Then we tested the measurement invariance of the C19P-SC across gender and time. Finally, the reliability was measured with the McDonald's omega coefficients. Consistent with previous studies, the C19P-SC showed a stable four-factor structure. The results showed that ESEM was better than CFA and more reasonable. In addition, the results of multi-group ESEM showed that the C19P-SC met the strict invariance at male and female and partial longitudinal strict invariance. The Mcdonald's omega coefficients of the C19P-SC total scale and each subscale reached the expected acceptable level. In short, the reliability and validity index of C19P-SC has reached an acceptable level, and the measurement invariance of different genders and different time points was established, but the cross-factor phenomenon of individual items was abnormal, and a further revision and testing are still needed.

Ultrafast and absolute quantification of SARS-CoV-2 on food using hydrogel RT-LAMP without pre-lysis.

With rapid growing of environmental contact infection, more and more attentions are focused on the precise and absolute quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus on cold chain foods via point-of-care test (POCT). In this work, we propose a hydrogel-mediated reverse transcription loop-mediated isothermal amplification (RT-LAMP) for ultrafast and absolute quantification of SARS-CoV-2. Cross-linked hydrogel offers opportunities for digital single molecule amplification in nanoconfined spaces, facilitating the virus lysis, RNA reverse transcription and amplification process, which is about 3.4-fold faster than conventional bulk RT-LAMP. Ultrafast quantification of SARS-CoV-2 is accomplished in 15 min without virus pre-lysis and RNA extraction. The sensitivity can accurately quantify SARS-CoV-2 down to 0.5 copy/µL. Furthermore, the integrated system has an excellent specificity, reproducibility and storage stability, which can be also used to test SARS-CoV-2 on various cold chain fruits. The developed ultrafast and simple hydrogel RT-LAMP will be an enormous potential for surveillance of virus or other hazardous microbes in environmental, agricultural and food industry.

Screening of cell-virus, cell-cell, gene-gene crosstalk among animal kingdom at single cell resolution.

BACKGROUND: The exact animal origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains obscure and understanding its host range is vital for preventing interspecies transmission. METHODS: Herein, we applied single-cell sequencing to multiple tissues of 20 species (30 data sets) and integrated them with public resources (45 data sets covering 26 species) to expand the virus receptor distribution investigation. While the binding affinity between virus and receptor is essential for viral infectivity, understanding the receptor distribution could predict the permissive organs and tissues when infection occurs. RESULTS: Based on the transcriptomic data, the expression profiles of receptor or associated entry factors for viruses capable of causing respiratory, blood, and brain diseases were described in detail. Conserved cellular connectomes and regulomes were also identified, revealing fundamental cell-cell and gene-gene cross-talks from reptiles to humans. CONCLUSIONS: Overall, our study provides a resource of the single-cell atlas of the animal kingdom which could help to identify the potential host range and tissue tropism of viruses and reveal the host-virus co-evolution.

Early identification and severity prediction of acute respiratory infection (ESAR): a study protocol for a randomized controlled trial.

BACKGROUND: The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored. METHODS: ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups. DISCUSSION: ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

Back Cover: Detection, prevention and treatment of COVID-19 and opportunities for nanobiotechnology (View 4/2022)

In article number 20200181, Chuanbin Mao, Mingying Yang and their co-wokers have demonstrated that nanobiotechnology holds promise for combating COVID-19. It provides nanoscale probes to detect COVID-19, nanoscale vaccines to prevent COVID-19, and nanoscale therapeutics to treat COVID-19. Because nanoparticles are comparable to the virus particles that cause COVID-19, the nanoparticles can be engineered to detect, prevent or treat COVID-19 in a more efficient manner than the other agents.

Rotavirus and Norovirus Infections in Children Under 5 Years Old with Acute Gastroenteritis in Southwestern China, 2018-2020.

OBJECTIVE: Rotaviruses and noroviruses are important causes of acute gastroenteritis in children. While previous studies in China have mainly focused on rotavirus, we investigated the incidence of norovirus in addition to rotavirus in Southwestern China. METHODS: From January 2018 to December 2020, cases of rotavirus or norovirus infections among children under five ages with acute gastroenteritis were evaluated retrospectively. RESULTS: The detection rate of rotavirus was 24.5% (27,237/111,070) and norovirus was 26.1% (4649/17,797). Among 17,113 cases submitted for dual testing of both rotavirus and norovirus, mixed rotavirus/norovirus infections were detected in 5.0% (859/17,113) of cases. While there was no difference in norovirus incidence in outpatient compared to hospitalized cases, rotavirus was detected two times more in outpatients compared to hospitalized cases (26.6% vs.13.6%; P < 0.001). Both rotavirus and norovirus infections peaked in children aged 12-18 months seeking medical care with acute gastroenteritis (35.6% rotavirus cases; 8439/23,728 and 32.5% norovirus cases; 1660/5107). Rotavirus infections were frequent between December and March of each year while norovirus was detected earlier from October to December. Our results showed significant correlation between virus detection and environmental factors such as average monthly temperature but not relative humidity. In addition, we observed a reduction in the detection rates of rotavirus and norovirus at the beginning of the SARS-CoV-2 pandemic in 2020. CONCLUSION: Our results indicate that rotavirus and norovirus are still important viral agents in pediatric acute gastroenteritis in Southwestern China.

Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L.

Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV, and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the spike proteins of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 µM for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 µM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.

A Systematic Survey of Physicians' Insights Into Lipohypertrophy.

Background: It is important that physicians be aware of LH. We designed a questionnaire to determine physician awareness, knowledge, and behaviors regarding LH in clinical practice. Participants: A total of 499 questionnaires were completed by physicians in hospitals from 13 cities in Jiangsu Province, China. Key Results: Compared with physicians at tertiary hospitals, significantly fewer physicians at primary hospitals reported awareness of LH and its screening methods. The proportion of resident physicians aware of LH was significantly lower than the proportion of senior physicians. The proportion of physicians who could identify all LH risk factors among the low-GDP group was significantly higher than the high-GDP group. Only 38.7% of doctors could successfully identify all the hazards associated with LH, but more doctors in tertiary hospitals were able to do so compared to those in secondary and primary hospitals. Compared with tertiary hospitals, the proportions of primary and secondary hospitals with management processes were significantly lower. The proportion of doctors who educated patients regarding LH prevention and treatment in primary hospitals was markedly lower than in tertiary hospitals. Conclusions: Overall, physicians have an inadequate understanding of LH, especially in primary hospitals.

Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load.

Despite extensive efforts, COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large. Vaccination is an effective approach to curb virus spread, but several variants (e.g., delta, delta plus, omicron, and IHU) appear to weaken or possibly escape immune protection. Thus, novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently needed. Multiple evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown mechanism. Here, we reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase (also known as nonstructural protein 12 (NSP12)) of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants, including omicron and IHU. Mechanistically, heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer. A mild daily heat treatment maintains low levels of both wild-type and P323L mutant of NSP12, suggesting clinical potential. Collectively, this novel mechanism, heat-induced NSP12 degradation, suggests a prospective heat-based intervention against SARS-CoV-2.

Detection, prevention and treatment of COVID-19 and opportunities for nanobiotechnology.

Since the outbreak of COVID-19, the number of confirmed cases and deaths has increased globally at a dramatic speed. In view of the serious health threat to humans, this review discusses the state-of-the-art studies about fighting this disease. It summarizes the current strategies and recent advances in detecting, preventing, and treating COVID-19 and interprets the underlying mechanisms in detail. Detection of COVID-19 can be successfully achieved by multiple techniques such as polymerase chain reaction, computed tomography imaging, and nano-biosensing. Inactivated virus vaccine, nucleic acid vaccine, and different nanoparticles have been employed to effectively prevent COVID-19. A variety of agents such as antiviral agents, neutralizing antibodies, and nanotherapeutics have been developed to treat COVID-19 with exciting efficacy. Although nanobiotechnology has shown great potential in the diagnosis, prevention, and treatment of COVID-19, efforts should be made to explore new biocompatible nano-biomaterials to advance this field to clinical applications. Hence, nanobiotechnology paves a new way to detect, prevent, and treat COVID-19 effectively.

Clinical efficacy and safety of acupuncture combined with western medicine in treatment of 3 cases of severe COVID-19

OBJECTIVE: To observe the clinical efficacy and safety of the intradermal acupuncture combined with western medicine treatment of three severe crona virus disease 2019 (COVID-19). METHODS: The clinical data of three severe COVID-19 confirmed patients were retrospectively analyzed.On the basis of conventional western medical treatment, intradermal embedding treatment was used for the Kongzu, Dazhui, and Feishu points. Lung CT reports of patients before and after treatment were compared, including the percentage of neutrophil, lymphocyte, hypersensitive C-reactive protein, oxygen index and other indicators. RESULTS: The three severe COVID-19 patients were discharged from hospital after treatment with significant relief of symptoms. Lung CT re-examination showed absorption of lesions and normal inflammatory indicators, and nucleic acid reexamination was negative. CONCLUSION: At present, elderly patients with severe COVID-19 have complicated conditions and high mortality. As an auxiliary means, intradermal acupuncture combined with western medicine therapy is simple, safe and effective in the treatment of severe COVID-19, which is a new exploration for the treatment of complicated COVID-19 conditions.